CHICAGO--(BUSINESS WIRE)--
Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced the
final results from a Phase 2a study of the investigational selective
oral JAK3 inhibitor VX-509. The data showed substantial and
statistically significant improvements in multiple measurements of
rheumatoid arthritis (RA) activity. The 12-week study met its two
primary endpoints, defined as a statistically significant improvement in
the proportion of people who achieved at least a 20 percent improvement
in the signs and symptoms of RA, also known as ACR20, and a
statistically significant improvement from baseline in Disease Activity
Score 28 (DAS28). For the two highest dose groups of the study,
statistically significant ACR20, ACR50, ACR70,
and DAS28 responses were also observed as compared to placebo, and more
than one-third of people in these groups achieved clinical remission
(DAS28 remission). Overall, the most frequently reported class of
adverse event in the VX-509 and placebo arms was infections. The data
from the study will be presented in a poster session on November 8 at
the 2011 Annual Meeting for the American College of Rheumatology (ACR)
in Chicago.

"People with RA experience frequent debilitating pain and discomfort in
joints, which significantly impacts their lives and underscores the need
for new RA medicines," said Roy Fleischmann, M.D., Clinical Professor of
Medicine at the University of Texas Southwestern Medical Center and an
investigator for the Phase 2 study of VX-509. "People in this study
showed significant improvement in the signs and symptoms of RA after
treatment with VX-509 — an encouraging step toward the future treatment
of RA by selectively targeting an underlying mechanism of the disease."

Based on the Phase 2a data to be presented at ACR, a six-month Phase 2b
study of VX-509 in RA is expected to begin in early 2012. This study,
which will be run by Vertex, will evaluate once-daily (QD) and
twice-daily (BID) doses of VX-509 in combination with methotrexate, a
commonly prescribed disease-modifying antirheumatic drug (DMARD) for RA
that is frequently used in combination with other RA medicines. The
study is expected to enroll approximately 350 people with moderate to
severe RA.

About the Phase 2a Study

This double-blind, randomized, placebo-controlled Phase 2a study of
VX-509 enrolled 204 people with active moderate to severe RA. The study
enrolled people who had an inadequate response to at least one currently
available non-biologic (non-injectable) DMARD. The study evaluated four
dose levels of VX-509, which was given twice daily (BID) for 12 weeks.
Patients did not receive methotrexate during this study, but could have
received it prior to the study. Approximately 40 clinical trial sites
participated in the trial in the United States and Europe. Vertex
reported top-line data from this study in September 2011.

Efficacy Data

The study met its two primary endpoints, which were the proportion of
people who achieved an ACR20 response at week 12 and the
change from baseline in DAS28 at week 12. Additional secondary endpoints
were used to evaluate the clinical activity of VX-509, including ACR50
and ACR70 responses at week 12, DAS28 remission and EULAR
response. The responses observed in the two highest dose groups for
VX-509 indicated continuous and statistically significant improvements
in the signs and symptoms of RA, with these effects being observed in
some patients as early as the first week of the study. Efficacy results
are provided below. ACR responses are based on an intent-to-treat
analysis where patients who discontinued treatment prior to week 12 were
counted as non-responders (failures) in the efficacy analyses,
regardless of their response to treatment:

American College of Rheumatology Responses at Week 12:

VX-509 (n=163)

ACR20

ACR50

ACR70

25 mg (n=41)

39%(p=0.485)

17%(p=0.312)

7%(p=0.616)

50 mg (n=41)

61%(p=0.007)

32%(p=0.011)

12%(p=0.201)

100 mg (n=40)

65%(p=0.002)

38%(p=0.001)

18%(p=0.029)

150 mg (n=41)

66%(p=0.002)

49%(p<0.001)

22%(p=0.014)

Placebo (n=41)

29%

7%

2%

Disease Activity Scores at Week 12:

VX-509

DAS28 Improvement from Baseline

25 mg

-1.75(p=0.155)

50 mg

-2.60(p<0.001)

100 mg

-2.70(p<0.001)

150 mg

-3.06(p<0.001)

Placebo

-1.25

DAS28 Remission:

The study also evaluated the proportion of patients in each treatment
arm who experienced clinical remission, defined as a patient with a
DAS28 score of less than 2.6 at week 12. In this study, 12 percent, 15
percent, 35 percent and 37 percent of people achieved DAS28 remission in
the 25 mg, 50 mg, 100 mg and 150 mg treatment groups, respectively,
compared to 7 percent of people in the placebo arm.

EULAR Response:

The study also evaluated the proportion of patients in each treatment
arm who experienced a good or moderate EULAR response. EULAR response is
calculated as a measurement of the absolute value and improvement in a
person's DAS28 score over time. EULAR responses were as follows:

VX-509

Good or Moderate EULAR Response

25 mg

59 percent of patients

50 mg

78 percent of patients**

100 mg

73 percent of patients*

150 mg

78 percent of patients**

Placebo

42 percent of patients

* p < 0.007 ** p ≤ 0.0001

Safety Data

At least 80 percent of all people in each of the VX-509 treatment groups
completed the 12-week treatment course, and 68 percent of people who
received placebo completed treatment. Treatment discontinuations due to
adverse events occurred in 5 percent of people in the placebo group
compared to 0 percent, 2 percent, 18 percent and 12 percent of people in
the 25 mg, 50 mg, 100 mg and 150 mg groups, respectively. Overall, the
most frequently reported class of adverse event in the VX-509 and
placebo arms was infections, which occurred in 17 percent of people who
received placebo and in 17 percent of people who received VX-509. The
most common individual adverse events were nausea (6 percent for the
VX-509 groups; 0 percent for placebo), increased alanine
aminotransferase (ALT) (4 percent for the VX-509 groups; 5 percent for
placebo) and headache (4 percent for the VX-509 groups; 5 percent for
placebo). Dose-related low-grade increases in high-density lipoprotein
(HDL) and low-density lipoprotein (LDL) cholesterol were observed in
people who received VX-509.

Serious adverse events occurred in 2 percent of people in the placebo
treatment group, compared to 0 percent, 2 percent 13 percent and 5
percent of people in the 25 mg, 50 mg, 100 mg and 150 mg VX-509 groups,
respectively. The most common serious adverse events in the VX-509
treatment arms were infections, which occurred in 0 percent of people in
the placebo treatment group, compared to 0 percent, 0 percent, 8 percent
and 5 percent of people in the 25 mg, 50 mg, 100 mg and 150 mg VX-509
groups, respectively. There were no serious adverse events related to
measurements in ALT.

As previously reported, in the 100 mg dose group of the study, one
patient died of a hemorrhagic stroke, reported as unrelated to VX-509.
Also in this dose group, one patient died of pneumonia. This patient
received VX-509 and other medicines also associated with a potential
increase in susceptibility to infections. As a result, a contribution of
VX-509 to the severity of the pneumonia in this patient cannot be ruled
out.

There were no meaningful declines observed in measures of hemoglobin or
neutrophils among people who received VX-509 compared to those who
received placebo. Two percent of all people who received VX-509
discontinued treatment due to lack of efficacy, compared to 15 percent
in the placebo group.

About VX-509

VX-509 is an investigational oral medicine being developed by Vertex
that is designed to selectively inhibit Janus kinase 3, or JAK3, which
is an essential part of the underlying disease mechanisms that cause
inflammation in diseases such as RA. JAK3 specific inhibition represents
a new approach to the treatment of a range of autoimmune diseases where
it is an essential component of the signaling cascade that contributes
to the abnormal immune response, which results in chronic inflammation
and, in the case of RA, irreversible damage to cartilage and bones. JAK3
is one of four JAK family kinases (JAK1, JAK2, JAK3 and Tyk2).

Based on in vitro data, VX-509 has demonstrated a high degree of
potency for JAK3 and a high level of selectivity for inhibition of JAK3
compared to JAK1 and JAK2 dependent assays. VX-509 has been shown to be
greater than 1000-fold more selective for JAK3 compared to non-JAK
kinases and approximately 25- to 150-fold more selective for JAK3
compared to other JAK isotypes in cell-based assays. This high level of
selectivity was confirmed in clinical studies where dose-related
inhibition of a JAK3 dependent biomarker was observed while little to no
effect was shown against a JAK2/JAK1 dependent biomarker.

About Rheumatoid Arthritis

RA is a chronic inflammatory disease that affects 1 percent to 2 percent
of the world's population, including 1.5 million adults in the United
States.1,9 The disease causes destruction of joint cartilage
and erosion of adjacent bone, resulting in deformity, loss of function,
substantial disability and, for many, the need for joint replacement.
Many people with RA suffer progressive disability over time,2,3
pain,4 work loss,5 substantial health care costs,6
and premature death.7 Approximately 80 percent of people with
RA become disabled within 20 years of diagnosis.8

The treatment of RA focuses on reducing symptoms and inhibiting
progression of the disease. Nonsteroidal anti-inflammatory drugs
(NSAIDs) and corticosteroids may reduce the symptoms of pain, swelling
and stiffness, but they do not alter the natural course of the disease.
Disease-modifying antirheumatic drugs (DMARDs) have shown effects in
slowing the progression of joint damage and time to disability and thus
altering the natural history of RA. While recently approved medicines
are effective in a portion of patients, a significant number of people
with RA do not respond adequately or become refractory to these
medicines, creating a significant need for new approaches to RA
treatment.

About Endpoints in RA:ACR and DAS Responses

The most common endpoints in RA clinical studies are ACR and DAS
responses. ACR responses are defined as the proportion of patients in a
trial who achieve at least a pre-specified percent improvement in the
signs and symptoms of RA, as measured by tender and swollen joint counts
and other criteria. For example, an ACR20 response reflects
the proportion of people who had at least a 20 percent improvement in
both tender and swollen joints in addition to improvements in other
criteria such as C-reactive protein (CRP), Health Assessment
Questionnaire (HAQ) disability scores and others. DAS responses,
including DAS28, are derived from an assessment of multiple measurements
of RA, including tender and swollen joints, C-reactive protein (CRP) and
a patient's assessment of general health.

About Vertex

Vertex creates new possibilities in medicine. Our team discovers,
develops and commercializes innovative therapies so people with serious
diseases can lead better lives.

Vertex scientists and our collaborators are working on new medicines to
cure or significantly advance the treatment of hepatitis C, cystic
fibrosis, rheumatoid arthritis, epilepsy and other life-threatening
diseases.

Founded more than 20 years ago in Cambridge, MA, we now have ongoing
worldwide research programs and sites in the U.S., U.K. and Canada.
Today, Vertex has more than 1,900 employees around the world, and Science
magazine named Vertex number one on its 2011 list of Top Employers in
the life sciences.

Special Note Regarding Forward-Looking Statements:

This press release contains forward-looking statements as defined in the
Private Securities Litigation Reform Act of 1995, including statements
regarding (i) the plan to begin in early 2012 a six-month Phase 2b trial
to evaluate VX-509 in approximately 350 people with RA; (ii) the
potential to treat RA by selectively targeting an underlying mechanism
of the disease; and (iii) the potential clinical trial design for the
planned Phase 2b trial. While Vertex believes the forward-looking
statements contained in this press release are accurate, these
statements are subject to risks and uncertainties that could cause
actual outcomes to vary materially from the outcomes referenced in the
forward-looking statements. These risks and uncertainties include, among
other things, the risks that efforts to develop VX-509 may not proceed
due to technical, scientific, commercial, financial or other reasons,
that a safety profile for VX-509 could be established in further
nonclinical studies or clinical trials that could put further
development of VX-509 in jeopardy or adversely effect its therapeutic
value, and other risks listed under Risk Factors in Vertex's annual
report and quarterly reports filed with the Securities and Exchange
Commission and available through the Vertex's website at www.vrtx.com.
Vertex disclaims any obligation to update the information contained in
this press release as new information becomes available.